Inhibition of Neuraminidase Inhibitor-Resistant Influenza Virus by DAS181, a Novel Sialidase Fusion Protein

Antiviral drug resistance for influenza therapies remains a concern due to the high prevalence of H1N1 2009 seasonal influenza isolates which display H274Y associated oseltamivir-resistance. Furthermore, the emergence of novel H1N1 raises the potential that additional reassortments can occur, resulting in drug resistant virus. Thus, additional antiviral approaches are urgently needed. DAS181 (Fludase®), a sialidase fusion protein, has been shown to have inhibitory activity against a large number of seasonal influenza strains and a highly pathogenic avian influenza (HPAI) strain (H5N1). Here, we examine the in vitro activity of DAS181 against a panel of 2009 oseltamivir-resistant seasonal H1N1 clinical isolates. The activity of DAS181 against nine 2009, two 2007, and two 2004 clinical isolates of seasonal IFV H1N1 was examined using plaque number reduction assay on MDCK cells. DAS181 strongly inhibited all tested isolates. EC50 values remained constant against isolates from 2004, 2007, and 2009, suggesting that there was no change in DAS181 sensitivity over time. As expected, all 2007 and 2009 isolates were resistant to oseltamivir, consistent with the identification of the H274Y mutation in the NA gene of all these isolates. Interestingly, several of the 2007 and 2009 isolates also exhibited reduced sensitivity to zanamivir, and accompanying HA mutations near the sialic acid binding site were observed. DAS181 inhibits IFV that is resistant to NAIs. Thus, DAS181 may offer an alternative therapeutic option for seasonal or pandemic IFVs that become resistant to currently available antiviral drugs

Simulated Sustained Flight Operations and Performance, Part 2: Effects of Dextro-Methamphetamine

As aircrew performance declines during periods of sustained flight operations (SUSOPs), countermeasures become more important. This study examined the ability of the central nervous system stimulant d-methamphetamine to ameliorate the detrimental effects of a simulated SUSOP on subjective fatigue and cognitive performance. Subjects (N = 25) repeatedly completed three subjective questionnaires and several subtests of the Unified Tri-Service Cognitive Performance Assessment Battery (UTC-PAB) and the Walter Reed Performance Assessment Battery (WR-PAB) during a simulated SUSOP. The scenario consisted of a 9-hr planning session followed by 4 hr of rest and a 14-hr mission. After 6 hr of rest, the 9 hr-4 hr-14 hr work-rest-work pattern was repeated. In a double-blind procedure, 13 subjects were administered 10mg/70kg body weight of d-methamphetamine 4 hr 20 min into the second mission, whereas the other 12 subjects received a placebo. Consistent with our preceding article in this series (Neri, Shappell, & DeJohn, 1992), the aircrew appeared to shift from a conservative to a more risky response strategy as the simulated SUSOP progressed. Administration of d-methamphetamine reduced subjective fatigue, improved performance, and lessened the apparent risky behavior on two spatial memory tasks

Featured Articles Efficacy of a medical food in mild Alzheimer's disease: A randomized, controlled trial

Abstract Objective: To investigate the effect of a medical food on cognitive function in people with mild Alzheimer's disease (AD). Methods: A total of 225 drug-naïve AD patients participated in this randomized, double-blind controlled trial. Patients were randomized to active product, Souvenaid, or a control drink, taken once-daily for 12 weeks. Primary outcome measures were the delayed verbal recall task of the Wechsler Memory Scale-revised, and the 13-item modified Alzheimer's Disease Assessment Scale-cognitive subscale at week 12. Results: At 12 weeks, significant improvement in the delayed verbal recall task was noted in the active group compared with control (P 5 .021). Modified Alzheimer's Disease Assessment Scale-cognitive subscale and other outcome scores (e.g., Clinician Interview Based Impression of Change plus Caregiver Input, 12-item Neuropsychiatric Inventory, Alzheimer's disease Co-operative Study-Activities of Daily Living, Quality of Life in Alzheimer's Disease) were unchanged. The control group neither deteriorated nor improved. Compliance was excellent (95%) and the product was well tolerated. Conclusions: Supplementation with a medical food including phosphatide precursors and cofactors for 12 weeks improved memory (delayed verbal recall) in mild AD patients. This proof-of-concept study justifies further clinical trials